CD4/CD8 Ratio and Cancer Risk among Adults with HIV

Jessica L. Castilho, Aihua Bian, Cathy A. Jenkins, Bryan E. Shepherd, Keith Sigel, M. John Gill, Mari M. Kitahata, Michael J. Silverberg, Angel M. Mayor, Sally B. Coburn, Dorothy Wiley, Chad J. Achenbach, Vincent C. Marconi, Ronald J. Bosch, Michael A. Horberg, Charles S. Rabkin, Sonia Napravnik, Richard M. Novak, W. Christopher Mathews, Jennifer E. ThorneJing Sun, Keri N. Althoff, Richard D. Moore, Timothy R. Sterling, Staci L. Sudenga

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Background: Independent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada. Methods: We examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness. Results: Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P <. 05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values. Conclusions: A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.

Original languageEnglish
Pages (from-to)854-862
Number of pages9
JournalJournal of the National Cancer Institute
Issue number6
StatePublished - 1 Jun 2022


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